Study of the Fed-Fast Pharmocokinetics and Bioequivalance of 300mg Capsules of Droxidopa

NCT01149629 | Completed Phase 1

• 1 other identifier: Droxidopa NOH101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

One purpose of this study is to determine if taking droxidopa after eating will have an effect on how the body processes (absorbs and eliminates) the drug in healthy elderly subjects. Another purpose of this study is to see how the body processes (absorbs and eliminates) one 300mg capsule compared to three 100mg capsules. This study will also evaluate how well the body processes (absorbs and eliminates) and tolerates droxidopa when a 300 mg capsule is given 3 times a day for a total dose of 900 mg over the course of one day. Droxidopa is used to treat low blood pressure upon standing in patients with diseases of the nervous system, to prevent low blood pressure in patients with kidney disease during hemodialysis (removal of waste products of the blood), and to treat frozen gait (walking, stepping or running) and dizziness upon standing in patients with Parkinson's disease.

Conditions

Symptomatic Neurogenic Orthostatic Hypotension

Keywords

Droxidopa; Randomized; Crossover; Open Label; Bioequivalence; Fed Fast; TID

Outcome Measures

Primary Outcomes (1)

• Droxidopa Pharmacokinetics

  Blood samples will be collected at the time from 0 to 24 hours. Cmax, Tmax, AUC(0-∞), AUC(0-t), t1/2, and CL/F, will be determined for plasma concentrations of droxidopa in Parts I and II and will also be determined for two of its metabolites (3-OM-droxidopa and norepinephrine) in Part II only.

  24 hours

Study Arms (4)

Fed Dosing

ACTIVE COMPARATOR

Subjects fed a high calorie, high fat meal prior to receiving 3 x 100mg capsules

Drug: Droxidopa

Fasted Dosing

ACTIVE COMPARATOR

Subjects fasted prior to receiving 3 x 100mg capsules

Drug: Droxidopa

Bioequivalence

ACTIVE COMPARATOR

Subjects fasted prior to receiving 1x 300mg capsule

Drug: Droxidopa

TID Dosing

ACTIVE COMPARATOR

Droxidopa 300 mg given TID

Drug: Droxidopa

Interventions

Droxidopa DRUG

One capsule containing 300 mg droxidopa, given once

Bioequivalence

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Provide written consent on an IRB-approved Informed Consent Form (ICF), prior to any study-specific evaluation. Subjects should have the ability to read and understand the ICF, ask for any clarifications from the study staff, and be able to comply with all planned study procedures.
• Male or female ≥65 years of age.
• Body mass index (BMI) between 18 and 35 kg/m2, inclusive.
• If female, not pregnant (or lactating), as evidenced by a negative serum pregnancy test, and is surgically sterile (hysterectomy, bilateral ovariectomy, or bilateral tubal ligation), or at least 2 years postmenopausal.
• Ability and willingness to abstain from alcohol from 48 h prior to the first dose until the completion of the study.
• No clinically significant abnormalities on the basis of medical history, physical examination, and vital signs unless currently controlled with medical treatment (e.g., a stable medication dosing regimen).
• Computerized, 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations, as judged by the investigator.
• All values for hematology, clinical chemistry, and urinalysis are normal or if abnormal-are deemed not clinically significant as judged by a physician investigator with documented agreement from the Medical Monitor.
• Nonsmoking or have quit smoking at least 6 months prior to dosing.

You may not qualify if:

• Presence of active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease not currently controlled with medical treatment (e.g., a stable medication dosing regimen).
• Presence of an active malignancy of any type other than nonmelanomatous skin malignancies.
• History of relevant drug and/or food allergies.
• Recent history (past 5 years) of alcohol abuse or drug addiction.
• Required use of concomitant medications that could confound the PK or safety evaluation, such as medications that affect GI function (including proton pump inhibitors or metoclopramide) or vasoconstricting agents (e.g., ephedrine, dihydroergotamine, or midodrine), -triptans (e.g., sumatriptan, naratriptan, zolmitriptan, rizatriptan), halogen-containing anesthetics (e.g., cyclopropane, or halothane), catecholaminecontaining preparations (e.g., isoprenaline), non-selective MAOIs, ergotamine derivatives (except for anti-Parkinson medications), or any drugs with anti-hypertensive properties that in the investigator's opinion, could significantly contribute to the subject's orthostatic hypotension.
• Participation in an investigational drug study within 30 days prior to study drug administration.
• Donated a unit of blood (500 mL) or plasma within the 30-day period prior to the initial dose of study medication or who intend to donate blood or plasma within a 30-day period following the final dose of study medication.
• Positive screen for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines) or alcohol.
• Positive screen for urine cotinine.
• Positive screen for hepatitis B surface antigen.
• Positive screen for antibodies to hepatitis C virus.
• Positive screen for antibodies to human immunodeficiency virus (HIV-1/HIV-2).
• Acute illness within 5 days prior to drug administration.
• History of coagulation disorder, thrombocytopenia, bleeding tendency, or gastrointestinal bleeding.
• Professional or ancillary personnel involved in the study.

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (1)

Cetero Research

Fargo, North Dakota, 58104, United States

Location

Related Publications (1)

• Chen JJ, Hewitt LA. Comparison of the Pharmacokinetics of Droxidopa After Dosing in the Fed Versus Fasted State and with 3-Times-Daily Dosing in Healthy Elderly Subjects. Drugs R D. 2018 Mar;18(1):77-86. doi: 10.1007/s40268-018-0226-z.

  PMID: 29392574 DERIVED

MeSH Terms

Interventions

Droxidopa

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Gregory M Haugen, M.D.

  Cetero Research, San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: June 23, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: March 20, 2013

Record last verified: 2013-03

Locations

US (1)